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7 Exercise 2 Compounding and Filtration Product being compounded/ formulated, filtered and filled into mobile 300l vessels. What design features should be considered to mimimise issues such as manual handling/ contamination for: A: Filling Area B: Vessel

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10 Process Stages 4. Container Preparation – Cleaning and Sterilisation of Empty product Containers Cleaning Washing and rinsing of containers using suitable grade of water to remove extraneous particles and chemicals Initial rinses can be carried out using Purified water Final rinse must use WFI (Water for injection) Containers blown dry using sterile air Equipment Rotary Washer Linear Washer

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17 Process Stages 5. Stopper Preparation Stoppers must be sterile as they are in direct contact with the product at some time during storage, handling or use Washing and rinsing to remove extraneous particulates and chemicals Detergent washing sometimes used for endotoxin load reduction Stopper may be siliconised for ease of insertion of stoppers into vials Stoppers must receive a final rinse of WFI Stoppers must be sterilised (typically using clean steam) Stoppers must be dried using sterile air Stoppers must maintain sterility during transfer to filler Equipment Rotating Drum Stopper Processor Fluidised Bed Stopper Processor

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18 Stopper Processor The stoppers are simply and quickly loaded through hatches in the drum The loaded drum is slid into the chamber on its carriage. As the door is hinged shut the magnetically coupled drive engages Fedegari (Modified Autoclave)

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21 Process Stages Contact Parts Preparation Equipment parts which come into contact with either the product or container closure components must be cleaned and sterilised before each batch, e.g. product filling vessel, filling pumps, stopper feed tracks Washing and rinsing with detergent to remove product residues Initial rinses with purified water Final rinse(s) with WFI Sterilised using steam in pass through autoclave Equipment Parts Washer Ultrasonic Bath Autoclave

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22 Process Stages - Autoclave

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23 Process Stages - Sterilisation Sterility Assurance Level (SAL) The probability of any given unit being non-sterile after exposure to a validated sterilisation process. Autoclaves generally obtain an SAL of (i.e. assurance of less than one chance in a million that viable micro- organisms are present in the sterilised article) To calculate the SAL for an autoclave, you need to know:- A: Starting bio-burden B: Log Reduction Valve (LRV) must be known. The LRV is the number of logarithmic reductions in initial count brought about by the autoclave (sterilisation method)

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32 Stoppering Application of Stoppers Usually by Means of Pick & Place Device Vibratory Bowl Used to Sort Stoppers Track-Feed Stoppers to Pick & Place Device Key Considerations Grade A / Class 100 / ISO 5 Condition Required Stopper / Closure Contact Surfaces should be a a Suitable Material and Finish to Prevent Contamination Movement & Stoppers and Vibratory Bowl make this an Area of Risk

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33 Process Stages Secures the Inserted Stopper into the Vial Neck Helping to Ensure Long- Term Integrity and Sterility of the Vial Caps can be Plastic or Aluminium Key Considerations Capping Machines are Contaminant producers as They Release Particles During Crimping Capper and Filler Usually in Different Rooms to Avoid Contamination Bosch 7. Capping and Crimping